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Insomnia severity and depressive symptoms in people living with HIV and chronic pain: associations with opioid use.

Chronic pain commonly occurs in people living with HIV (PLWH). Many PLWH in the United States obtain opioids for chronic pain management. Whether insomnia severity and depressive symptoms are exacerbated by chronic pain and opioid use in PLWH remains to be determined. This study examined insomnia severity and depressive symptoms in 85 PLWH with chronic pain and 35 PLWH without chronic pain. Among PLWH with chronic pain, reported opioid use was examined in relation to insomnia severity and depressive symptoms. PLWH with chronic pain reported significantly greater insomnia severity ( = .033) and depressive symptoms ( = .025) than PLWH without chronic pain. Among PLWH with chronic pain who reported opioid use ( = 36), insomnia severity was greater compared to those who denied opioid use ( = 49), even after controlling for pain severity and number of comorbidities ( = .026). Greater pain severity was significantly associated with greater insomnia severity ( < .001) and depressive symptoms ( = .048) among PLWH with chronic pain who reported opioid use. These associations were not significant among those PLWH with chronic pain who denied opioid use. Findings suggest that PLWH with chronic pain are likely to experience poor sleep and depressed mood. Furthermore, poor sleep was associated with opioid use among PLWH with chronic pain.

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Challenges and opportunities in translational pain research – An opinion paper of the working group on translational pain research of the European pain federation (EFIC).

For decades, basic research on the underlying mechanisms of nociception has held promise to translate into efficacious treatments for patients with pain. Despite great improvement in the understanding of pain physiology and pathophysiology, translation to novel, effective treatments for acute and chronic pain has however been limited, and they remain an unmet medical need. In this opinion paper bringing together pain researchers from very different disciplines, the opportunities and challenges of translational pain research are discussed. The many factors that may prevent the successful translation of bench observations into useful and effective clinical applications are reviewed, including interspecies differences, limited validity of currently available preclinical disease models of pain, and limitations of currently used methods to assess nociception and pain in non-human and human models of pain. Many paths are explored to address these issues, including the backward translation of observations made in patients and human volunteers into new disease models that are more clinically relevant, improved generalization by taking into account age and sex differences, and the integration of psychobiology into translational pain research. Finally, it is argued that preclinical and clinical stages of developing new treatments for pain can be improved by better preclinical models of pathological pain conditions alongside revised methods to assess treatment-induced effects on nociception in human and non-human animals. Significance: For decades, basic research of the underlying mechanisms of nociception has held promise to translate into efficacious treatments for patients with pain. Despite great improvement in the understanding of pain physiology and pathophysiology, translation to novel, effective treatments for acute and chronic pain has however been limited, and they remain an unmet medical need.

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Do chronic low back pain subgroups derived from dynamic quantitative sensory testing exhibit differing multidimensional profiles?

The relationship of pain sensitivity with pain and disability in low back pain (LBP) is complicated. It has been suggested increased understanding of dynamic quantitative sensory testing (QST) might be useful in increasing understanding of these relationships. This study aimed to create subgroups based on participant responses to dynamic QST, profile these subgroups based on multidimensional variables (including clinical measures of pain and disability, psychological and lifestyle variables and static QST), and investigate the association of subgroup membership with levels of pain intensity, LBP-related disability and disability risk at 12-month follow up.

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‘External timing’ of placebo analgesia in an experimental model of sustained pain.

Research on placebo analgesia commonly focuses on the impact of information about direction (i.e. increase or decrease of pain) and magnitude of the expected analgesic effect whereas temporal aspects of expectations have received little attention so far. In a recent study using short-lasting, low-intensity stimuli we demonstrated that placebo analgesia onset is influenced by temporal information. Here, we investigate whether the same effect of temporal suggestions can be found in longer lasting, high-intensity pain in a Cold Pressor Test (CPT).

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Pain Prevalence, Chronicity and Impact within Subpopulations Based on Both Hispanic Ancestry and Race: United States, 2010-2017.

We provide national surveillance estimates of pain chronicity, severity and impact in adult subpopulations defined by both Hispanic Ancestry and Race. Data are from 144,434 adults who completed validated questionnaires in the 2010-2017 National Health Interview Survey asking about pain status within the last three (n=84,664) or six months (n=59,770). Multivariable logistic regression was used to assess the relationship between pain and ethnicity/race. Compared to White Puerto Rican participants, White participants with Central/South American and Mexican ancestry had reduced odds of reporting Category 3-4 pain and High-Impact Chronic Pain (HICP), while those of Cuban ancestry had reduced odds of only HICP – e.g., White participants with Mexican ancestry had 32% lower odds of having Category 3-4 pain and 50% lower odds of having HICP. While no differences were seen between White Puerto Rican and White Non-Hispanic participants for Category 3-4 pain, White Non-Hispanics had 40% lower odds of reporting HICP. Asian Non-Hispanic and Black Non-Hispanic participants had significantly lower odds of reporting Category 3-4 pain and HICP compared to White Puerto Rican participants, e.g., Black Non-Hispanic participants had 26% lower odds off having Category 3-4 pain and 42% lower odds of having HICP. Perspective: By examining pain status in discrete demographic groups based on Hispanic Ancestry and Race, this report further documents substantial differences in health status among underserved populations and provides a baseline for continuing surveillance research on pain, with the eventual goal of eliminating disparities in pain assessment and treatment.

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Development and Validation of the Brief Assessment of Distress about Pain.

The experience of pain is a complex interaction of somatic, behavioral, affective, and cognitive components. Negative psychological states (e.g., anxiety, fear, and depression) are intertwined with pain and contribute to poorer outcomes for individuals suffering from chronic and acute pain by exacerbating the overall experience of pain and leading to increased dysfunction, disability, and distress. A need exists for efficient assessment of aversive emotional states that are associated with pain.

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Nociceptor Overexpression of Na1.7 Contributes to Chronic Muscle Pain Induced by Early-Life Stress.

Adult rats previously submitted to neonatal limited bedding (NLB), a model of early-life stress, display muscle mechanical hyperalgesia and nociceptor hyperexcitability, the underlying mechanism for which is unknown. Since voltage-gated sodium channel subtype 7 (Na1.7) contributes to mechanical hyperalgesia in several preclinical pain models and is critical for nociceptor excitability, we explored its role in the muscle hyperalgesia exhibited by adult NLB rats. Western blot analyses demonstrated increased Na1.7 protein expression in L4-L5 dorsal root ganglia (DRG) from adult NLB rats, and antisense oligodeoxynucleotide (AS ODN) targeting Na1.7 alpha subunit mRNA attenuated the expression of Na1.7 in DRG extracts. While this AS ODN did not affect nociceptive threshold in normal rats it significantly attenuated hyperalgesia in NLB rats. The selective Na1.7 activator OD1 produced dose-dependent mechanical hyperalgesia that was enhanced in NLB rats, whereas the Na1.7 blocker ProTx-II prevented OD1-induced hyperalgesia in control rats and ongoing hyperalgesia in NLB rats. AS ODN knockdown of extracellular signal-regulated kinase 1/2, which enhances Na1.7 function, also inhibited mechanical hyperalgesia in NLB rats. Our results support the hypothesis that overexpression of Na1.7 in muscle nociceptors play a role in chronic muscle pain induced by early-life stress, suggesting that Na1.7 is a target for the treatment of chronic muscle pain. PERSPECTIVE: We demonstrate that early-life adversity, induced by exposure to inconsistent maternal care, produces chronic muscle hyperalgesia, which depends, at least in part, on increased expression of Na1.7 in nociceptors.

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Long-term outcomes of children with severe chronic pain: Comparison of former patients with a community sample.

Findings on the short- and long-term effectiveness of intensive interdisciplinary pain treatment (IIPT) for children with severe chronic functional pain are promising. However, a definitive appraisal of long-term effectiveness cannot be made due to a lack of comparison groups. The aim of the present study was to compare the health status of former patients with the health status of an age- and sex-matched comparison group from the community.

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Prospective associations of frequent pain symptoms with suicidal behavior in adolescents.

Chronic pain and suicidal behavior are prevalent in adolescents. This longitudinal study examined the associations between pain symptoms and suicidal behavior in adolescents. A total of 7,072 adolescents participated in a follow-up study of behavior and health in Shandong, China. A self-administered structured questionnaire was used to assess pain symptoms (headache, stomachache, and other nonspecific pain), insomnia, anxiety/depression, substance use, stressful life events, prior suicidal behavior, and family environment in November-December in 2015. One year later, a follow-up survey was conducted. Mean age of the sample was 14.6 years, and half were female. Of the sample, 44.8% and 8.4% reported having one or more pain symptoms "sometimes" and "often", respectively. A total of 22.4% and 10.6% reported having lifetime suicidal behavior at baseline and subsequent suicidal behavior over the 1-year follow-up, respectively. Frequent pain was significantly associated with increased risk of suicidal behavior at baseline (OR=1.64, 95%CI=1.32-2.03) and during the subsequent year (OR=1.50, 95%CI=1.17-1.93) while adjusting for covariates. Among adolescents without a history of prior suicidal behavior, frequent pain was significantly associated with an approximately 70% increased risk of incident suicidal behavior (OR= 1.69, 95%CI=1.14-2.51). In conclusion, frequent pain appears to be predictive of adolescent suicidal behavior while adjusting for family and personal psychosocial covariates. PERSPECTIVE: This article presents the prospective associations of frequent pain symptoms with suicidal behavior in adolescents. Frequent pain was associated with a 50-70% increased risk of suicidal behavior 1 year later. The finding underscores the importance of pain assessment and treatment in comprehensive suicide prevention efforts in adolescents.

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Genetic priming of sensory neurons in mice that overexpress PAR2 enhances allergen responsiveness.

Pruritus is a common symptom of inflammatory skin conditions, including atopic dermatitis (AD). Although primary sensory neurons that transmit pruritic signals are well-cataloged, little is known about the neuronal alterations that occur as a result of skin disruption in AD. To address this question, we examined the molecular and behavioral consequences of challenging mice, which overexpress PAR2 in suprabasal keratinocytes, with serial topical application of the environmental allergen house dust mite (HDM). We monitored behavior and used RNA sequencing, qPCR, and in situ hybridization to evaluate gene expression in trigeminal ganglia (TG), before and after HDM. We found that neither nor wild-type (WT) mice exhibited spontaneous scratching, and pruritogen-induced acute scratching did not differ. In contrast, HDM exacerbated scratching in mice. Despite the absence of scratching in untreated mice, several TG genes in these mice were up-regulated compared to WT. HDM treatment of the mice enhanced up-regulation of this set of genes and induced additional genes, many within the subset of TG neurons that express TRPV1. The same set of genes was up-regulated in HDM-treated mice that did not scratch, but at lesser magnitude. Finally, we recorded comparable transcriptional changes in IL31Tg mice, demonstrating that a common genetic program is induced in two AD models. Taken together, we conclude that transcriptional changes that occur in primary sensory neurons in dermatitis-susceptible animals underlie a genetic priming that not only sensitizes the animal to chronic allergens but also contributes to pruritus in atopic skin disease.

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